FeverPhase 4NCT02294071
Prospective Comparative Study of the Efficacy of Common Antipyretic Treatments in Febrile Children
A Phase 4 study testing Ibuprofen and Acetaminophen in people with Fever, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's.
Trial summary
This study will examine in detail the immediate effects of three common treatments given to children with fevers to lower their temperature. Each child will be given either ibuprofen, acetaminophen, or a combination, and their temperature monitored at five-minute intervals. Read more about this study
- Who is it for?
- Ages 3 to 12 years
- Conditions the study is for
- Fever
- What is being tested?
- Ibuprofen and Acetaminophen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- Dec 2014to Nov 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- fever between 38 and 41 Celsius (inclusive) on presentation to ER
- assessment by treating physician that patient requires antipyretic treatment
Who cannot join
- known allergy or hypersensitivity to either study medication
- received any antipyretic medication in past eight hours
- patient requires admission to hospital
- co-morbidities indicating increased risk of complication
- assessment by treating physician that patient is medically unsuitable for the study
Trial locations and contacts
No sites are listed yet.
About this study
This study will examine in detail the immediate effects of three common treatments given to children with fevers to lower their temperature. Each child will be given either ibuprofen, acetaminophen, or a combination, and their temperature monitored at five-minute intervals. The temperature-lowering effects of each treatment will be compared to evaluate which is most effective.
Read the detailed description
There is no substantial evidence that a fever lower than 41°C is harmful to the welfare of an otherwise healthy child, although they can be dangerous to children already in critical condition [1,2]. However, fevers in healthy children commonly cause anxiety in parents and caregivers, so parents and physicians often give antipyretic medications to lower the fever [3,4]. Ibuprofen and acetaminophen are two of the most commonly used medications in children. Most major pediatric medical associations agree about appropriate dosages for children, but give no clear guidelines on whether ibuprofen or acetaminophen should be used [3,5]. Physicians commonly make the decision between the two based on their personal opinions of the efficacy and safety of the medications, or based on habit [6]. Survey data shows that more than half of physicians use combinations of both acetaminophen and ibuprofen to treat fever, either simultaneously or on an alternating schedule, with a variety of dosing patterns [6]. A majority of physicians believed there were established guidelines supporting this use, but in fact there are not [6].
Combining the two medications is widely theorized to improve effectiveness, but clinical trials comparing combination treatments to ibuprofen and/or acetaminophen alone have shown inconsistent results [4,7-12]. Several pharmacodynamic studies have shown that ibuprofen and acetaminophen both produce their largest effects on temperature within the first hour following dosage [9,10,13-16]. Despite this, only one study has been performed examining the change in temperature at intervals shorter than 30 minutes, and that study used substandard monitoring methods [10].
This study will use gold-standard monitoring methods to take temperatures every five minutes through the first one to four hours of treatment. Understanding the pattern of temperature change in the acute stages after dosing will help settle the debate about the optimal medication choice for treating childrens' fevers.
- Conditions
- Fever
- Being tested
- Ibuprofen, Acetaminophen
- Keywords
- acetaminophen, ibuprofen
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbuprofenDrug
Also called Advil
oral liquid ibuprofen 10mg/kg (maximum 600 mg)
AcetaminophenDrug
Also called Tylenol
oral liquid acetaminophen 15mg/kg (max 975mg)
| Study group | Role | What they receive |
|---|---|---|
| acetaminophen | Experimental | acetaminophen 15mg/kg (max 975mg) Receives: Drug: Acetaminophen |
| ibuprofen | Experimental | ibuprofen 10mg/kg (max 600mg) Receives: Drug: Ibuprofen |
| combination | Experimental | acetaminophen 15mg/kg (max 975mg) and ibuprofen 10mg/kg (max 600mg) Receives: Drug: Ibuprofen; Drug: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
temperature reduction from baseline
change in temperature from baseline at time of drug administration and at five minute intervals afterward for a minimum of one hour, maximum 4 hours
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study startDec 2014
- Primary completionNov 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Rieder, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Michael J Rieder, MD, Principal investigator, Western University, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02294071
- Sponsor's protocol ID
- LHRI IRF
- Status last verified
- Nov 2014
- First submitted
- 17 Nov 2014
- Last updated
- 19 Nov 2014
- Results posted
- No
Publications
Mullins ME, Empey M, Jaramillo D, Sosa S, Human T, Diringer MN. A prospective randomized study to evaluate the antipyretic effect of the combination of acetaminophen and ibuprofen in neurological ICU patients. Neurocrit Care. 2011 Dec;15(3):375-8. doi: 10.1007/s12028-011-9533-8.
PubMed 21503807Lee BH, Inui D, Suh GY, Kim JY, Kwon JY, Park J, Tada K, Tanaka K, Ietsugu K, Uehara K, Dote K, Tajimi K, Morita K, Matsuo K, Hoshino K, Hosokawa K, Lee KH, Lee KM, Takatori M, Nishimura M, Sanui M, Ito M, Egi M, Honda N, Okayama N, Shime N, Tsuruta R, Nogami S, Yoon SH, Fujitani S, Koh SO, Takeda S, Saito S, Hong SJ, Yamamoto T, Yokoyama T, Yamaguchi T, Nishiyama T, Igarashi T, Kakihana Y, Koh Y; Fever and Antipyretic in Critically ill patients Evaluation (FACE) Study Group. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Crit Care. 2012 Feb 28;16(1):R33. doi: 10.1186/cc11211.
PubMed 22373120Section on Clinical Pharmacology and Therapeutics; Committee on Drugs; Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. 2011 Mar;127(3):580-7. doi: 10.1542/peds.2010-3852. Epub 2011 Feb 28.
PubMed 21357332Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database Syst Rev. 2013 Oct 30;2013(10):CD009572. doi: 10.1002/14651858.CD009572.pub2.
PubMed 24174375D Leduc SWCPSCPC. Temperature measurement in pediatrics. Canadian Pediatric Society. 2013.
Mayoral CE, Marino RV, Rosenfeld W, Greensher J. Alternating antipyretics: is this an alternative? Pediatrics. 2000 May;105(5):1009-12. doi: 10.1542/peds.105.5.1009.
PubMed 10790455Vyas FI, Rana DA, Patel PM, Patel VJ, Bhavsar RH. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Perspect Clin Res. 2014 Jan;5(1):25-31. doi: 10.4103/2229-3485.124567.
PubMed 24551584Allan GM, Ivers N, Shevchuk Y. Treatment of pediatric fever: Are acetaminophen and ibuprofen equivalent? Can Fam Physician. 2010 Aug;56(8):773. No abstract available.
PubMed 20705883Erlewyn-Lajeunesse MD, Coppens K, Hunt LP, Chinnick PJ, Davies P, Higginson IM, Benger JR. Randomised controlled trial of combined paracetamol and ibuprofen for fever. Arch Dis Child. 2006 May;91(5):414-6. doi: 10.1136/adc.2005.087874. Epub 2006 Feb 7.
PubMed 16464962Hay AD, Costelloe C, Redmond NM, Montgomery AA, Fletcher M, Hollinghurst S, Peters TJ. Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial. BMJ. 2008 Sep 2;337:a1302. doi: 10.1136/bmj.a1302.
PubMed 18765450Kramer LC, Richards PA, Thompson AM, Harper DP, Fairchok MP. Alternating antipyretics: antipyretic efficacy of acetaminophen versus acetaminophen alternated with ibuprofen in children. Clin Pediatr (Phila). 2008 Nov;47(9):907-11. doi: 10.1177/0009922808319967. Epub 2008 Jun 6.
PubMed 18539869Paul IM, Sturgis SA, Yang C, Engle L, Watts H, Berlin CM Jr. Efficacy of standard doses of Ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children. Clin Ther. 2010 Dec;32(14):2433-40. doi: 10.1016/j.clinthera.2011.01.006.
PubMed 21353111Brown RD, Kearns GL, Wilson JT. Integrated pharmacokinetic-pharmacodynamic model for acetaminophen, ibuprofen, and placebo antipyresis in children. J Pharmacokinet Biopharm. 1998 Oct;26(5):559-79. doi: 10.1023/a:1023225217108.
PubMed 10205771Kauffman RE, Sawyer LA, Scheinbaum ML. Antipyretic efficacy of ibuprofen vs acetaminophen. Am J Dis Child. 1992 May;146(5):622-5. doi: 10.1001/archpedi.1992.02160170102024.
PubMed 1621668Temple AR, Temple BR, Kuffner EK. Dosing and antipyretic efficacy of oral acetaminophen in children. Clin Ther. 2013 Sep;35(9):1361-75.e1-45. doi: 10.1016/j.clinthera.2013.06.022. Epub 2013 Aug 23.
PubMed 23972576
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Comparative Study of the Efficacy of Common Antipyretic Treatments in Febrile Children
- ClinicalTrials.gov ID
- NCT02294071
- Acronym / sponsor ID
- LHRI IRF
- Conditions
- Fever
- Keywords
- acetaminophen, ibuprofen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Nov 2015 (estimated)
- First posted
- 19 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine in detail the immediate effects of three common treatments given to children with fevers to lower their temperature. Each child will be given either ibuprofen, acetaminophen, or a combination, and their temperature monitored at five-minute intervals. The temperature-lowering effects of each treatment will be compared to evaluate which is most effective.
Detailed description
There is no substantial evidence that a fever lower than 41°C is harmful to the welfare of an otherwise healthy child, although they can be dangerous to children already in critical condition [1,2]. However, fevers in healthy children commonly cause anxiety in parents and caregivers, so parents and physicians often give antipyretic medications to lower the fever [3,4]. Ibuprofen and acetaminophen are two of the most commonly used medications in children. Most major pediatric medical associations agree about appropriate dosages for children, but give no clear guidelines on whether ibuprofen or acetaminophen should be used [3,5]. Physicians commonly make the decision between the two based on their personal opinions of the efficacy and safety of the medications, or based on habit [6]. Survey data shows that more than half of physicians use combinations of both acetaminophen and ibuprofen to treat fever, either simultaneously or on an alternating schedule, with a variety of dosing patterns [6]. A majority of physicians believed there were established guidelines supporting this use, but in fact there are not [6].
Combining the two medications is widely theorized to improve effectiveness, but clinical trials comparing combination treatments to ibuprofen and/or acetaminophen alone have shown inconsistent results [4,7-12]. Several pharmacodynamic studies have shown that ibuprofen and acetaminophen both produce their largest effects on temperature within the first hour following dosage [9,10,13-16]. Despite this, only one study has been performed examining the change in temperature at intervals shorter than 30 minutes, and that study used substandard monitoring methods [10].
This study will use gold-standard monitoring methods to take temperatures every five minutes through the first one to four hours of treatment. Understanding the pattern of temperature change in the acute stages after dosing will help settle the debate about the optimal medication choice for treating childrens' fevers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| acetaminophen | Experimental | Drug: Acetaminophenacetaminophen 15mg/kg (max 975mg) |
| ibuprofen | Experimental | Drug: Ibuprofenibuprofen 10mg/kg (max 600mg) |
| combination | Experimental | Drug: Ibuprofen, Drug: Acetaminophenacetaminophen 15mg/kg (max 975mg) and ibuprofen 10mg/kg (max 600mg) |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- fever between 38 and 41 Celsius (inclusive) on presentation to ER
- assessment by treating physician that patient requires antipyretic treatment
Key exclusion criteria (5 listed)
- known allergy or hypersensitivity to either study medication
- received any antipyretic medication in past eight hours
- patient requires admission to hospital
- co-morbidities indicating increased risk of complication
- assessment by treating physician that patient is medically unsuitable for the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbuprofenAlso: Adviloral liquid ibuprofen 10mg/kg (maximum 600 mg) | Drug | combination, ibuprofen |
| AcetaminophenAlso: Tylenoloral liquid acetaminophen 15mg/kg (max 975mg) | Drug | acetaminophen, combination |
Primary outcome
temperature reduction from baseline
Time frame: 4 hours
change in temperature from baseline at time of drug administration and at five minute intervals afterward for a minimum of one hour, maximum 4 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2014.
- Background: PubMed 21503807Mullins ME, Empey M, Jaramillo D, Sosa S, Human T, Diringer MN. A prospective randomized study to evaluate the antipyretic effect of the combination of acetaminophen and ibuprofen in neurological ICU patients. Neurocrit Care. 2011 Dec;15(3):375-8. doi: 10.1007/s12028-011-9533-8.
- Background: PubMed 22373120Lee BH, Inui D, Suh GY, Kim JY, Kwon JY, Park J, Tada K, Tanaka K, Ietsugu K, Uehara K, Dote K, Tajimi K, Morita K, Matsuo K, Hoshino K, Hosokawa K, Lee KH, Lee KM, Takatori M, Nishimura M, Sanui M, Ito M, Egi M, Honda N, Okayama N, Shime N, Tsuruta R, Nogami S, Yoon SH, Fujitani S, Koh SO, Takeda S, Saito S, Hong SJ, Yamamoto T, Yokoyama T, Yamaguchi T, Nishiyama T, Igarashi T, Kakihana Y, Koh Y; Fever and Antipyretic in Critically ill patients Evaluation (FACE) Study Group. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Crit Care. 2012 Feb 28;16(1):R33. doi: 10.1186/cc11211.
- Background: PubMed 21357332Section on Clinical Pharmacology and Therapeutics; Committee on Drugs; Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. 2011 Mar;127(3):580-7. doi: 10.1542/peds.2010-3852. Epub 2011 Feb 28.
- Background: PubMed 24174375Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database Syst Rev. 2013 Oct 30;2013(10):CD009572. doi: 10.1002/14651858.CD009572.pub2.
- BackgroundD Leduc SWCPSCPC. Temperature measurement in pediatrics. Canadian Pediatric Society. 2013.
- Background: PubMed 10790455Mayoral CE, Marino RV, Rosenfeld W, Greensher J. Alternating antipyretics: is this an alternative? Pediatrics. 2000 May;105(5):1009-12. doi: 10.1542/peds.105.5.1009.
- Background: PubMed 24551584Vyas FI, Rana DA, Patel PM, Patel VJ, Bhavsar RH. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Perspect Clin Res. 2014 Jan;5(1):25-31. doi: 10.4103/2229-3485.124567.
- Background: PubMed 20705883Allan GM, Ivers N, Shevchuk Y. Treatment of pediatric fever: Are acetaminophen and ibuprofen equivalent? Can Fam Physician. 2010 Aug;56(8):773. No abstract available.
- Background: PubMed 16464962Erlewyn-Lajeunesse MD, Coppens K, Hunt LP, Chinnick PJ, Davies P, Higginson IM, Benger JR. Randomised controlled trial of combined paracetamol and ibuprofen for fever. Arch Dis Child. 2006 May;91(5):414-6. doi: 10.1136/adc.2005.087874. Epub 2006 Feb 7.
- Background: PubMed 18765450Hay AD, Costelloe C, Redmond NM, Montgomery AA, Fletcher M, Hollinghurst S, Peters TJ. Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial. BMJ. 2008 Sep 2;337:a1302. doi: 10.1136/bmj.a1302.
- Background: PubMed 18539869Kramer LC, Richards PA, Thompson AM, Harper DP, Fairchok MP. Alternating antipyretics: antipyretic efficacy of acetaminophen versus acetaminophen alternated with ibuprofen in children. Clin Pediatr (Phila). 2008 Nov;47(9):907-11. doi: 10.1177/0009922808319967. Epub 2008 Jun 6.
- Background: PubMed 21353111Paul IM, Sturgis SA, Yang C, Engle L, Watts H, Berlin CM Jr. Efficacy of standard doses of Ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children. Clin Ther. 2010 Dec;32(14):2433-40. doi: 10.1016/j.clinthera.2011.01.006.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael J Rieder, MD principal investigator
Western University, Canada
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ibuprofen and Acetaminophen in people with Fever, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael J Rieder, MD ((519) 685-8500 ext. 58293, mrieder@uwo.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
temperature reduction from baseline (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02294071, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2014.